ALDOSTERONE BIOSYNTHESIS IN THE RAT-BRAIN

Messenger RNA (mRNA) for enzymes involved in adrenal steroid biosynthe sis are expressed in the brain, and the coded enzymes have been shown to be active. The expression of mRNA for the cytochrome P-450 enzyme a ldosterone synthase, crucial for the final step in the synthesis of al dosterone and the synthesis of aldosterone was studied in several anat omic areas of the rat brain. Expression of the mRNA for the aldosteron e synthase was demonstrated by RT-PCR/Southern blot in adrenal, aorta, hypothalamus, hippocampus, amygdala, cerebrum, and cerebellum. Incuba tion of brain minces from intact and adrenalectomized rats demonstrate d the synthesis of corticosterone and aldosterone from endogenous prec ursors. Incubations of brain minces with [1,2(3)H]-deoxycorticosterone , followed by extraction and three different successive TLCs, demonstr ated the presence of labeled aldosterone, corticosterone, and 18-hydro xy-deoxycorticosterone. Incubation, in the presence of 10 mu M cortiso l or metyrapone, inhibited the synthesis of aldosterone or both aldost erone and corticosterone, respectively. These studies indicate that th e rat brain has the enzymatic machinery for the synthesis of adrenal c orticosteroids and is capable of synthesizing aldosterone. Aldosterone synthesized in the brain might play a paracrine role in the regulatio n of blood pressure.